Many biologic functions are dictated by the primary structure of proteins. Our ability to understand these functions has been limited by our ability to understand these structures. Over the past few years, methods have been developed which allow the application of protein sequence analysis to a variety of major biologic questions. The nature and sites of protein polymorphism, of chemical modification and of substrate binding give insights into the way in which molecules function. A number of NIH-supported projects on the Georgetown University campus are examining the structure-function relationship for proteins involved in immune response, proteins involved in chromatin/DNA interaction and proteins alterated during chemotherapy. These studies include the biochemistry of: (1) Human histocompatibility antigens encoded by the HLS-D region. (2) Poly (ADP-ribose) polymerase as it relates to chromatin structure and function. (3) Cobra venon factor as it relates to the human complement component C3b. (4) DNA endonucleases. (5) Intracellular proteins as modified by nitrosourea, an antitumor drug. Each of these studies requires the use of a protein sequencer. This proposal constitutes a request by members of Georgetown University to purchase this sequencer. This sequencer will be an important tool in defining protein primary structure so that an understanding of protein function can be obtained.